We are now directing our studies of hereditary diabetes in the mouse to answer several questions. We are studying juvenile diabetics, 4 days of age and younger, to determine whether the hypersecretion in vitro of pancreatic alpha-2 beta cells represents an intrinsic pancreatic expression of the gene, diabetes, or reflects prior stimulation in vitro by the hypothalamus-pituitary-adrenal endocrine axis. We have initiated an ultrastructural study of the nature of beta cell atrophy versus hyperplasia as a function of diabetes gene expression on different genetic backgrounds. We have begun examining the role of the somatostatin-containing alpha-1 cell as a regulator of islet secretory activity. Finally, we shall use ultrastructural biochemical techniques to question whether the association of oncornavirus with hyperplastic or pathological disease states of the pancreas is causal or coincidental.